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1.
Eur J Neurol ; 28(2): 717-725, 2021 02.
Article in English | MEDLINE | ID: mdl-33043544

ABSTRACT

Stroke is the second leading cause of death and dependency in Europe and costs the European Union more than €30bn, yet significant gaps in the patient pathway remain and the cost-effectiveness of comprehensive stroke care to meet these needs is unknown. The European Brain Council Value of Treatment Initiative combined patient representatives, stroke experts, neurological societies and literature review to identify unmet needs in the patient pathway according to Rotterdam methodology. The cost-effectiveness of comprehensive stroke services was determined by a Markov model, using UK cost data as an exemplar and efficacy data for prevention of death and dependency from published systematic reviews and trials, expressing effectiveness as quality-adjusted life-years (QALYs). Model outcomes included total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). Key unmet needs in the stroke patient pathway included inadequate treatment of atrial fibrillation (AF), access to neurorehabilitation and implementation of comprehensive stroke services. In the Markov model, full implementation of comprehensive stroke services was associated with a 9.8% absolute reduction in risk of death of dependency, at an intervention cost of £9566 versus £6640 for standard care, and long-term care costs of £35 169 per 5.1251 QALYS vs. £32 347.40 per 4.5853 QALYs, resulting in an ICER of £5227.89. Results were robust in one-way and probabilistic sensitivity analyses. Implementation of comprehensive stroke services is a cost-effective approach to meet unmet needs in the stroke patient pathway, to improve acute stroke care and support better treatment of AF and access to neurorehabilitation.


Subject(s)
Atrial Fibrillation , Stroke , Cost-Benefit Analysis , Europe , Humans , Markov Chains , Quality-Adjusted Life Years , Stroke/therapy
2.
Infect Genet Evol ; 85: 104453, 2020 11.
Article in English | MEDLINE | ID: mdl-32649994

ABSTRACT

Endometrial pathogenic E. coli (EnPEC) isolates are involved in endometrial infections in animals and humans. Besides the high aggressiveness of the endometrial infections, the EnPEC virulence profile and pathogenesis are still little known. In this study, we have sequenced and analyzed an EnPEC strain from canine pyometra (E. coli_LBV005/17), following a molecular characterization of the virulence profile and phylogenetic evolution of an EnPEC collection from canines and felines (45 strains). Most of the strains belonged to phylo-group B2, and display a high virulence profile. In particular we highlight the classification of the E. coli_LBV005/17 as sequence type 131 (ST131), in addition to other five strains, as observed by gyrB phylogenetic analysis. Also, the phylogenetic position of EnPEC strains from pyometra in companion animals suggests that their origins are from both extraintestinal and commensal E. coli strains. Accordingly to Principal Coordinates Analysis (PCoA) and phylogenetic analysis we can propose that EnPEC strains have neither the same genetic profile, nor a unique common ancestral. In summary, the present work characterize an EnPEC genome from bitch pyometra and the genetic profile of 45 EnPEC strains from companion animals pyometra, being the commonest virulence pattern: fimA, papC, hlyA, hlyE, cnf1, entB, iroN, irp1, bssS, bssR, and hmsP. These data improving the background knowledge of this E. coli pathotype related to pyometra in companion animals and may support new methods to prevent the disease evolution.


Subject(s)
Endometrium/microbiology , Escherichia coli Infections/microbiology , Escherichia coli Infections/veterinary , Escherichia coli/genetics , Pyometra/microbiology , Virulence Factors/genetics , Virulence , Animals , Anti-Bacterial Agents/pharmacology , Cat Diseases/microbiology , Cats , Dog Diseases/microbiology , Dogs , Escherichia coli/drug effects , Escherichia coli/pathogenicity , Female , Genome, Bacterial , Genotype , Humans , Microbial Sensitivity Tests , Pets/microbiology , Phylogeny
3.
Mater Sci Eng C Mater Biol Appl ; 107: 110243, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31761159

ABSTRACT

In this work, dextran based membranes with potential to be used as implantable devices in Tissue Engineering and Regenerative Medicine (TERM) were prepared by a straightforward strategy. Briefly, two polymers approved by the Food and Drug Administration, viz. dextran and poly(ε-caprolactone) (PCL) were functionalized with methacrylate moieties, and subjected to photocrosslinking. Employing different weight ratios of each polymer in the formulations allowed to obtain transparent membranes with tunable physicochemical properties and low adverse host tissue response. Independently of the material, all formulations have shown to be thermally stable up to 300 °C whilst variations in the polymer ratio resulted in membranes with different glass transition temperatures (Tg) and flexibility. The swelling capacity ranged from 50% to 200%. On the other hand, in vitro hydrolytic degradation did not show to be material-dependent and all membranes maintained their structural integrity for more than 30 days, losing only 8-12% of their initial weight. Preliminary in vitro biological tests did not show any cytotoxic effect on seeded human dental pulp stem cells (hDPSCs), suggesting that, in general, all membranes are capable of supporting cell adhesion and viability. The in vivo biocompatibility of membranes implanted subcutaneously in rats' dorsum indicate that M100/0 (100%wt dextran) and M25/75 (25 %wt dextran) formulations can be classified as "slight-irritant" and "non-irritant", respectively. From the histological analysis performed on the main tissue organs it was not possible to detect any signs of fibrosis or necrosis thereby excluding the presence of toxic degradation by-products deposited or accumulated in these tissues. In combination, these results suggest that the newly developed formulations hold great potential as engineered devices for biomedical applications, where the biological response of cells and tissues are greatly dependent on the physical and chemical cues provided by the substrate.


Subject(s)
Biocompatible Materials/chemistry , Dextrans/chemistry , Membranes, Artificial , Animals , Biocompatible Materials/metabolism , Biocompatible Materials/pharmacology , Calcium/metabolism , Cell Adhesion/drug effects , Cell Survival/drug effects , Dental Pulp/cytology , Humans , Male , Methacrylates/chemistry , Polyesters/chemistry , Prostheses and Implants , Rats , Rats, Sprague-Dawley , Stem Cells/cytology , Stem Cells/metabolism , Subcutaneous Tissue/metabolism , Subcutaneous Tissue/pathology
4.
Clin Immunol ; 200: 43-54, 2019 03.
Article in English | MEDLINE | ID: mdl-30735729

ABSTRACT

Immune systems have evolved to recognize and eliminate pathogens and damaged cells. In humans, it is estimated to recognize 109 epitopes and natural selection ensures that clonally expanded cells replace unstimulated cells and overall immune cell numbers remain stationary. But, with age, it faces continuous repertoire restriction and concomitant accumulation of primed cells. Changes shaping the aging immune system have bitter consequences because, as inflammatory responses gain intensity and duration, tissue-damaging immunity and inflammatory disease arise. During inflammation, the glycolytic flux cannot cope with increasing ATP demands, limiting the immune response's extent. In diabetes, higher glucose availability stretches the glycolytic limit, dysregulating proteostasis and increasing T-cell expansion. Long-term hyperglycemia exerts an accumulating effect, leading to higher inflammatory cytokine levels and increased cytotoxic mediator secretion upon infection, a phenomenon known as diabetic chronic inflammation. Here we review the etiology of diabetic chronic inflammation and its consequences on wound healing.


Subject(s)
Diabetes Mellitus/immunology , Diabetic Foot/immunology , Immunosenescence/immunology , Inflammation/immunology , Wound Healing/immunology , Cytokines/immunology , Humans , Hyperglycemia/immunology , T-Lymphocytes/immunology
5.
Biochim Biophys Acta Mol Basis Dis ; 1864(6 Pt A): 2183-2198, 2018 06.
Article in English | MEDLINE | ID: mdl-29625179

ABSTRACT

BACKGROUND: Cardiovascular diseases (CVDs) are leading cause of death and primary cause of morbidity and mortality in diabetic population. Epicardial adipose tissue (EAT) covers the heart's surface and is a source of biomolecules regulating heart and blood vessel physiology. The protective activation of the unfolded protein response (UPR) and autophagy allows the cardiomyocyte reticular network to restore energy and/or nutrient homeostasis and to avoid cell death. However, an excessive or prolonged UPR activation can trigger cell death. UPR activation is an early event of diabetic cardiomyopathies and deregulated autophagy is associated with CVDs. RESULTS: An upregulation of UPR markers (glucose-regulated protein 78 KDa, glucose-regulated protein 94 KDa, inositol-requiring enzyme 1α, protein kinase RNA-like ER kinase and CCAAT/-enhancer-binding protein homologous protein (CHOP) gene) in EAT compared to subcutaneous adipose tissue (SAT), was observed as well as the UPR-related apoptosis marker caspase-4/procaspase-4 ratio but not in CHOP protein levels. Additionally, levels of ubiquitin and ubiquitinated proteins were decreased in EAT. Moreover, upregulation of autophagy markers (5' adenosine monophosphate-activated protein kinase, mechanistic target of rapamycin, Beclin 1, microtubule-associated protein light chain 3-II, lysosome-associated membrane protein 2, and PTEN-induced putative kinase 1) was observed, as well as an increase in the apoptotic Bim but not the ratio between Bim and the anti-apoptotic Bcl-2 in EAT. Diabetic patients show alterations in UPR activation markers but not in autophagy or apoptosis markers. CONCLUSION: UPR and autophagy are increased in EAT compared to SAT, opening doors to the identification of early biomarkers for cardiomyopathies and novel therapeutic targets.


Subject(s)
Diabetes Mellitus/metabolism , Diabetic Cardiomyopathies/pathology , Heart Failure/pathology , Pericardium/metabolism , Proteostasis , Subcutaneous Fat/metabolism , Aged , Apoptosis , Autophagy , Biomarkers , Diabetes Mellitus/pathology , Diabetic Cardiomyopathies/diagnosis , Diabetic Cardiomyopathies/metabolism , Endoplasmic Reticulum/pathology , Endoplasmic Reticulum Stress , Female , Heart Failure/diagnosis , Heart Failure/metabolism , Humans , Male , Myocytes, Cardiac/pathology , Pericardium/cytology , Pericardium/pathology , Subcutaneous Fat/cytology , Unfolded Protein Response
6.
J Dent Res ; 97(8): 917-927, 2018 07.
Article in English | MEDLINE | ID: mdl-29499125

ABSTRACT

The chronic inflammatory immune response triggered by the infection of the tooth root canal system results in the local upregulation of RANKL, resulting in periapical bone loss. While RANKL has a well-characterized role in the control of bone homeostasis/pathology, it can play important roles in the regulation of the immune system, although its possible immunoregulatory role in infectious inflammatory osteolytic conditions remains largely unknown. Here, we used a mouse model of infectious inflammatory periapical lesions subjected to continuous or transitory anti-RANKL inhibition, followed by the analysis of lesion outcome and multiple host response parameters. Anti-RANKL administration resulted in arrest of bone loss but interfered in the natural immunoregulation of the lesions observed in the untreated group. RANKL inhibition resulted in an unremitting proinflammatory response, persistent high proinflammatory and effector CD4 response, decreased regulatory T-cell (Treg) migration, and lower levels of Treg-related cytokines IL-10 and TGFb. Anti-RANKL blockade impaired the immunoregulatory process only in early disease stages, while the late administration of anti-RANKL did not interfere with the stablished immunoregulation. The impaired immunoregulation due to RANKL inhibition is characterized by increased delayed-type hypersensitivity in vivo and T-cell proliferation in vitro to the infecting bacteria, which mimic the effects of Treg inhibition, reinforcing a possible influence of RANKL on Treg-mediated suppressive response. The adoptive transfer of CD4+FOXp3+ Tregs to mice receiving anti-RANKL therapy restored the immunoregulatory capacity, attenuating the inflammatory response in the lesions, reestablishing normal T-cell response in vivo and in vitro, and preventing lesion relapse upon anti-RANKL therapy cessation. Therefore, while RANKL inhibition efficiently limited the periapical bone loss, it promoted an unremitting host inflammatory response by interfering with Treg activity, suggesting that this classic osteoclastogenic mediator plays a role in immunoregulation.


Subject(s)
Osteolysis/immunology , Periapical Diseases/immunology , RANK Ligand/immunology , T-Lymphocytes, Regulatory/immunology , Adoptive Transfer , Alveolar Bone Loss/immunology , Alveolar Bone Loss/microbiology , Animals , Antibodies, Monoclonal/pharmacology , Cell Proliferation/drug effects , Cell Survival , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gene Expression , Immunity, Mucosal , Inflammation/immunology , Inflammation/microbiology , Infliximab/pharmacology , Interleukin-10/immunology , Lymphocyte Activation/drug effects , Male , Mice , Mice, Inbred C57BL , Osteolysis/microbiology , Periapical Diseases/microbiology , RANK Ligand/antagonists & inhibitors , Real-Time Polymerase Chain Reaction , Transforming Growth Factor beta/immunology
7.
Eur J Neurol ; 25(3): 425-433, 2018 03.
Article in English | MEDLINE | ID: mdl-29218822

ABSTRACT

BACKGROUND AND PURPOSE: The reduction of delay between onset and hospital arrival and adequate pre-hospital care of persons with acute stroke are important for improving the chances of a favourable outcome. The objective is to recommend evidence-based practices for the management of patients with suspected stroke in the pre-hospital setting. METHODS: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to define the key clinical questions. An expert panel then reviewed the literature, established the quality of the evidence, and made recommendations. RESULTS: Despite very low quality of evidence educational campaigns to increase the awareness of immediately calling emergency medical services are strongly recommended. Moderate quality evidence was found to support strong recommendations for the training of emergency medical personnel in recognizing the symptoms of a stroke and in implementation of a pre-hospital 'code stroke' including highest priority dispatch, pre-hospital notification and rapid transfer to the closest 'stroke-ready' centre. Insufficient evidence was found to recommend a pre-hospital stroke scale to predict large vessel occlusion. Despite the very low quality of evidence, restoring normoxia in patients with hypoxia is recommended, and blood pressure lowering drugs and treating hyperglycaemia with insulin should be avoided. There is insufficient evidence to recommend the routine use of mobile stroke units delivering intravenous thrombolysis at the scene. Because only feasibility studies have been reported, no recommendations can be provided for pre-hospital telemedicine during ambulance transport. CONCLUSIONS: These guidelines inform on the contemporary approach to patients with suspected stroke in the pre-hospital setting. Further studies, preferably randomized controlled trials, are required to examine the impact of particular interventions on quality parameters and outcome.


Subject(s)
Emergency Medical Services/standards , Stroke/therapy , Consensus , Emergency Medical Technicians , Humans , Neurology , Stroke/diagnosis
8.
Eur J Neurol ; 24(6): 755-761, 2017 06.
Article in English | MEDLINE | ID: mdl-28418189

ABSTRACT

BACKGROUND AND PURPOSE: Intravenous alteplase (rtPA) may be associated with seizures and epileptic activity in the electroencephalogram (EEG). The aim of this work was to compare the frequency of seizures and EEG abnormalities between stroke patients treated and not treated with rtPA. METHODS: This was a prospective study of consecutive acute anterior circulation ischaemic stroke patients, with 1-year follow-up. Patients were previously independent, had an admission National Institute of Health Stroke Scale score ≥4, an acute ischaemic lesion and no previous seizures. They received standardized diagnostic and medical care. A video-EEG was performed in 72 h (first EEG); during admission (daily until day 7 and after that if neurological worsening); at discharge and 1 year after stroke. RESULTS: In all, 151 patients (101 treated with rtPA) were included. The frequency of acute and remote symptomatic seizures was not significantly different between rtPA treated and non-treated patients (P = 0.726 and P = 0.748, respectively). Clinical paroxysmal phenomena during rtPA perfusion were observed in five (5%) patients. In the first EEG, rtPA treated patients more often had background diffuse slowing (43.6% vs. 26.0%, P = 0.036). This difference was no longer observed at discharge (24.0% vs. 19.1%, P = 0.517) nor 1 year after (11.8% vs. 10.0%, P = 0.765). No differences were found in the frequency of epileptiform (P = 0.867) or periodic discharges (P = 0.381). CONCLUSIONS: Intravenous alteplase is not associated with an increased risk of clinical or electroencephalographic epileptic phenomena.


Subject(s)
Epilepsy/chemically induced , Fibrinolytic Agents/adverse effects , Seizures/chemically induced , Stroke/drug therapy , Tissue Plasminogen Activator/adverse effects , Administration, Intravenous , Aged , Electroencephalography , Female , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Prospective Studies , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome
9.
J Laryngol Otol ; 131(2): 144-149, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27974068

ABSTRACT

OBJECTIVE: To describe the results obtained with endolymphatic sac drainage in patients with Ménière's disease. METHOD: A retrospective case review study was conducted of 95 Ménière's disease patients who underwent endolymphatic sac drainage in a tertiary care referral centre, after failing a long course of medical management. The main outcome measures were vertigo control and hearing preservation. RESULTS: In patients with unilateral disease, vertigo control was obtained in 94.3 per cent of patients. A significant improvement in cochlear function was seen in 14 per cent of patients, and hearing was preserved or improved in 88 per cent. For the bilateral group, vertigo control was obtained in 85.7 per cent of patients and cochlear function improved in 28 per cent. Hearing preservation was attained in 71 per cent of these patients. CONCLUSION: Endolymphatic sac drainage is a good surgical option for patients with incapacitating endolymphatic hydrops, providing a high percentage of vertigo control and hearing preservation.


Subject(s)
Endolymphatic Sac/surgery , Meniere Disease/surgery , Vertigo/physiopathology , Adult , Aged , Drainage , Endolymphatic Hydrops/surgery , Female , Hearing , Humans , Male , Meniere Disease/physiopathology , Middle Aged , Retrospective Studies , Treatment Outcome
10.
Acta Neurol Scand ; 135(3): 339-345, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27098844

ABSTRACT

OBJECTIVES: Language recovery following acute stroke is difficult to predict due to several evaluation factors and time constraints. We aimed to investigate the predictors of aphasia recovery and to identify the National Institute of Health and Stroke Scale (NIHSS) items that best reflect linguistic performance, 1 week after thrombolysis. MATERIALS AND METHODS: We retrieved data from a prospective registry of patients with aphasia secondary to left middle cerebral artery (MCA) stroke treated with intravenous thrombolysis. Complete recovery at day 7 (D7) was measured in a composite verbal score (CVS) (Σ Language+Questions+Commands NIHSS scores). Lesion size was categorized by the Alberta Stroke Program Early CT score (ASPECTS) and vascular patency by ultrasound. CVS was correlated with standardized aphasia testing if both were performed within a two-day interval. RESULTS: Of 228 patients included (age average 67.32 years, 131 men), 72% presented some language improvement that was complete in 31%. Total recovery was predicted by ASPECTS (OR=1.65; 95% CI, 1.295-2.108; P < 0.00) and baseline aphasia severity (OR=0.439; 95% CI, 0.242-0.796; P < 0.007). CVS correlated better with standardized aphasia measures (aphasia quotient, severity, comprehension) than NIHSS_Language item. CONCLUSIONS: Lesion size and initial aphasia severity are the main predictors of aphasia recovery one week after thrombolysis. A NIHSS composite verbal score seems to capture the global linguistic performance better than the language item alone.


Subject(s)
Aphasia/drug therapy , Fibrinolytic Agents/pharmacology , Outcome Assessment, Health Care , Registries , Stroke/drug therapy , Adult , Aged , Aged, 80 and over , Aphasia/etiology , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle Aged , Stroke/complications
11.
Eur J Neurol ; 22(4): 618-23, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25597418

ABSTRACT

In about a quarter of ischaemic strokes the cause is undetermined, because the investigation is incomplete or delayed, because there are multiple causes or because the stroke is truly cryptogenic. Cryptogenic stroke can be further classified as non-embolic or embolic. Embolic stroke of undetermined source can be due to paroxysmal atrial fibrillation, minor emboligenic cardiac conditions, atheroembolism, cancer associated and paradoxical embolism through a patent foramen ovale (PFO) or less often a pulmonary fistula. Currently, risk factor control, statins and antiplatelets are the main therapeutic measures to prevent recurrent stroke. There is no evidence to implement routine closure of PFO in patients with cryptogenic stroke. Direct anticoagulants are being evaluated in randomized controlled trials including embolic stroke of undetermined source patients. Advances in high resolution ultrasound or magnetic resonance imaging of extracranial and intracranial vessels and of the heart and prolonged heart rhythm monitoring will be instrumental techniques to identify arterial and cardiac hidden causes of stroke.


Subject(s)
Stroke , Humans , Stroke/diagnosis , Stroke/etiology , Stroke/therapy
12.
J Dairy Sci ; 98(1): 395-405, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25465561

ABSTRACT

Selection for hybrids with greater starch and NDF digestibility may be beneficial for dairy producers. The objective of this study was to determine the effect of feeding a TMR containing a floury-leafy corn silage hybrid (LFY) compared with a brown midrib corn silage hybrid (BMR) for intake, lactation performance, and total-tract nutrient digestibility in dairy cows. Ninety-six multiparous Holstein cows, 105±31d in milk at trial initiation, were stratified by DIM and randomly assigned to 12 pens of 8 cows each. Pens were randomly assigned to 1 of 2 treatments, BMR or LFY, in a completely randomized design; a 2-wk covariate period with cows fed a common diet followed by a 14-wk treatment period with cows fed their assigned treatment diet. Starch digestibilities, in situ, in vitro, and in vivo, were greater for LFY compared with BMR; the opposite was observed for NDF digestibility. Cows fed BMR consumed 1.7kg/d more dry matter than LFY. Although, actual-, energy-, and solids-corrected milk yields were greater for BMR than LFY, feed conversions (kg of milk or component-corrected milk per kg of DMI) did not differ. Fat-corrected milk and milk fat yield were similar, as milk fat content was greater for cows fed LFY (4.05%) than BMR (3.83%). Cows fed BMR had lower milk urea nitrogen concentration, but greater milk protein and lactose yields compared with LFY. Body weight change and condition score were unaffected by treatment. Total-tract starch digestibility was greater for cows fed the LFY corn silage; however, dry matter intake and milk and protein yields were greater for cows fed the BMR corn silage. Although total-tract starch digestibility was greater for cows fed the LFY corn silage, feed efficiency was not affected by hybrid type due to greater dry matter intake and milk and protein yields by cows fed the BMR corn silage.


Subject(s)
Cattle/physiology , Dietary Fiber/metabolism , Lactation/physiology , Milk/metabolism , Starch/metabolism , Zea mays/chemistry , Animal Nutritional Physiological Phenomena , Animals , Detergents , Diet/veterinary , Digestion , Female , Silage
13.
Oncogenesis ; 3: e123, 2014 Oct 20.
Article in English | MEDLINE | ID: mdl-25329722

ABSTRACT

The tumor microenvironment has a dynamic and usually cancer-promoting function during all tumorigenic steps. Glioblastoma (GBM) is a fatal tumor of the central nervous system, in which a substantial number of non-tumoral infiltrated cells can be found. Astrocytes neighboring these tumor cells have a particular reactive phenotype and can enhance GBM malignancy by inducing aberrant cell proliferation and invasion. The tumor suppressor p53 has a potential non-cell autonomous function by modulating the expression of secreted proteins that influence neighbor cells. In this work, we investigated the role of p53 on the crosstalk between GBM cells and astrocytes. We show that extracellular matrix (ECM) from p53(+/-) astrocytes is richer in laminin and fibronectin, compared with ECM from p53(+/+) astrocytes. In addition, ECM from p53(+/-) astrocytes increases the survival and the expression of mesenchymal markers in GBM cells, which suggests haploinsufficient phenotype of the p53(+/-) microenvironment. Importantly, conditioned medium from GBM cells blocks the expression of p53 in p53(+/+) astrocytes, even when DNA was damaged. These results suggest that GBM cells create a dysfunctional microenvironment based on the impairment of p53 expression that in turns exacerbates tumor endurance.

14.
Phys Rev Lett ; 113(10): 102502, 2014 Sep 05.
Article in English | MEDLINE | ID: mdl-25238352

ABSTRACT

The exact four-body equations of Alt, Grassberger, and Sandhas are solved for neutron-3He and proton-3H scattering in the energy regime above the four-nucleon breakup threshold. Cross sections and spin observables for elastic, transfer, charge-exchange, and breakup reactions are calculated using realistic nucleon-nucleon interaction models, including the one with effective many-nucleon forces due to explicit Δ-isobar excitation. The experimental data are described reasonably well with only few exceptions such as vector analyzing powers.

15.
J Dairy Sci ; 97(6): 3855-9, 2014.
Article in English | MEDLINE | ID: mdl-24746133

ABSTRACT

Microbial protein represents the majority of metabolizable protein absorbed by ruminant animals. Enhanced understanding of the AA digestibility of rumen microbes will improve estimates of metabolizable protein. The objective of this experiment was to determine the digestibility of AA in fluid- (FAB) and particle-associated bacteria (PAB) using the precision-fed cecectomized rooster bioassay. Bacteria were isolated from 4 ruminally cannulated lactating Holstein cows by differential centrifugation, including particle suspension in 0.1% Tween-80 for increased removal of PAB from ruminal digesta. Samples of FAB and PAB were fed to 9 cecectomized roosters to determine standardized digestibility of AA. Total AA digestibility was 76.8 and 75.5% for FAB and PAB, respectively, but did not differ. Differences existed in AA digestibilities within bacterial type when compared with the mean essential AA digestibility value. Compared with previous literature estimates of AA digestibility in microbes (mean = 76%; range = 57-87%) and relative to National Research Council estimates of total AA from rumen bacteria (80%), the precision-fed cecectomized rooster assay is an acceptable in vivo model to determine AA digestibility of rumen bacteria.


Subject(s)
Amino Acids/metabolism , Animal Feed/analysis , Bacteria/metabolism , Cattle/physiology , Digestion , Rumen/microbiology , Animal Nutritional Physiological Phenomena , Animals , Biological Assay/veterinary , Cattle/microbiology , Cecum/metabolism , Cecum/microbiology , Cecum/surgery , Chickens/metabolism , Male
16.
J Neuroendocrinol ; 26(3): 176-85, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24528254

ABSTRACT

In addition to cognitive decline, Alzheimer's disease (AD) patients also exhibit an unexplained weight loss that correlates with disease progression. In young and middle-aged AD patients, large amounts of amyloid-ß (Aß) deposits were observed in the hypothalamus, a brain region involved in the control of feeding and body weight through the action of peripheral metabolic peptides, which have recently been shown to have neuroprotective effects. Moreover, levels of peripheral metabolic peptides, such as leptin and ghrelin, are changed in AD patients. The present study aimed to investigate the role of Aß peptide in the survival of hypothalamic cells and to explore the receptor-mediated protective effect of leptin and ghrelin against Aß-induced toxicity in these cells. Using the mHypoE-N42 cell line, we demonstrated for the first time that oligomeric Aß is toxic to hypothalamic cells, leading to cell death. It was also demonstrated that leptin and ghrelin protect these cells against AßO-induced cell death through the activation of the leptin and ghrelin receptors, respectively. Furthermore, ghrelin and leptin prevented superoxide production, calcium rise and mitochondrial dysfunction triggered by AßO. Taken together, these results suggest that peripheral metabolic peptides, in particular leptin and ghrelin, might be considered as preventive strategies for ameliorating hypothalamic alterations in AD.


Subject(s)
Amyloid beta-Peptides/toxicity , Biopolymers/toxicity , Ghrelin/pharmacology , Hypothalamus/drug effects , Leptin/pharmacology , Peptide Fragments/toxicity , Amyloid beta-Peptides/antagonists & inhibitors , Animals , Calcium/metabolism , Cell Line , Hypothalamus/cytology , Hypothalamus/metabolism , Membrane Potential, Mitochondrial , Mice , Peptide Fragments/antagonists & inhibitors , Reactive Oxygen Species/metabolism
17.
Cell Death Dis ; 4: e789, 2013 Sep 05.
Article in English | MEDLINE | ID: mdl-24008733

ABSTRACT

Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within the central nervous system. The mechanisms underlying the pathogenesis of OA, and in particular how amyloid triggers neuronal damage, are still unknown. Here, we show that amyloid fibrils formed by a mutant form of TTR, A25T, activate microglia, leading to the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide. Further, we found that A25T amyloid fibrils induce the activation of Akt, culminating in the translocation of NFκB to the nucleus of microglia. While A25T fibrils were not directly toxic to neurons, the exposure of neuronal cultures to media conditioned by fibril-activated microglia caused synapse loss that culminated in extensive neuronal death via apoptosis. Finally, intracerebroventricular (i.c.v.) injection of A25T fibrils caused microgliosis, increased brain TNF-α and IL-6 levels and cognitive deficits in mice, which could be prevented by minocycline treatment. These results indicate that A25T fibrils act as pro-inflammatory agents in OA, activating microglia and causing neuronal damage.


Subject(s)
Amyloid Neuropathies, Familial/pathology , Memory Disorders/pathology , Memory, Short-Term , Microglia/pathology , Prealbumin/metabolism , Synapses/metabolism , Amyloid , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/physiopathology , Animals , Brain/metabolism , Cell Death/drug effects , Cell Nucleus/metabolism , Cells, Cultured , Culture Media, Conditioned/pharmacology , Disease Models, Animal , Endocytosis , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Inflammation Mediators/metabolism , Interleukin-6/metabolism , Memory Disorders/complications , Memory Disorders/physiopathology , Memory, Short-Term/drug effects , Mice , Microglia/drug effects , Microglia/metabolism , Minocycline/pharmacology , Mutation/genetics , NF-kappa B/metabolism , Neurons/drug effects , Neurons/metabolism , Phosphorylation , Protein Transport , Proto-Oncogene Proteins c-akt/metabolism , Synapses/drug effects , Tumor Necrosis Factor-alpha/metabolism
19.
Acta Neurol Scand ; 128(4): 235-40, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23464981

ABSTRACT

BACKGROUND: Studies suggest that N-terminal-pro-brain natriuretic peptide (NT-proBNP) can be a biomarker of cardioembolic stroke. However, the best time to measure it after stroke is unknown. We studied the time course of NT-proBNP in patients with ischemic stroke. METHODS: Consecutive acute ischemic stroke patients were admitted over 10 months to a Stroke Unit. Stroke type was classified according to TOAST. Blood samples were drawn within 24, 48, and 72 hours after stroke. Friedman test was used to compare NT-proBNP values across the 3 times in all, cardioembolic and non-cardioembolic stroke patients. Post hoc analysis with Wilcoxon signed-rank tests was conducted with a Bonferroni correction. Mann-Whitney test was used to compare median values of NT-proBNP between cardioembolic and non-cardioembolic stroke patients. ROC curves were drawn to determine NT-proBNP accuracy to diagnose cardioembolic stroke at 24, 48, and 72 hours after stroke onset. RESULTS: One hundred and one patients were included (29 cardioembolic) with a mean age of 64.5±12.3 years. NT-proBNP values for cardioembolic stroke were significantly higher (P < 0.001) than for non-cardioembolic stroke in the 3 time points. NT-proBNP was highest in the first 24-48 h after ischemic stroke and decreased significantly 72 h after stroke onset. The area under the curve for the three time points was similar. CONCLUSION: NT-proBNP levels were highest in the first 2 days after ischemic stroke and declined significantly thereafter. However, the area under the curve for the three time points was similar. The first 72 hours after ischemic stroke have a similar diagnostic accuracy to diagnose cardioembolic stroke.


Subject(s)
Brain Ischemia/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Stroke/blood , Adult , Aged , Aged, 80 and over , Area Under Curve , Brain/diagnostic imaging , Brain/pathology , Brain Ischemia/complications , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Observation , Prospective Studies , ROC Curve , Radiography , Statistics, Nonparametric , Stroke/etiology , Stroke/pathology , Time Factors , Tomography Scanners, X-Ray Computed
20.
Cerebrovasc Dis ; 35(2): 175-81, 2013.
Article in English | MEDLINE | ID: mdl-23429170

ABSTRACT

BACKGROUND: In case of spontaneous cervical artery dissection (CAD), a medical treatment with anticoagulant or antiplatelet (AP) drugs would avoid the occurrence of an ischemic stroke. Although immediate anticoagulation (AC) is advocated, evidence from randomized trials is lacking. Since CAD is characterized by a mural accumulation of blood, the dissecting hematoma may enlarge under AC, with subsequent lumen narrowing. Although direct evidence of mural hematoma enlargement is lacking in the literature, such a complication may not only be theoretical. Magnetic resonance imaging (MRI) of the mural hematoma on transverse sections through the neck is the current diagnostic gold standard. Our aim was to compare the evolution of the mural hematoma in CAD during the first week after treatment initiation (AP agent: groupAP, AC: groupAC), using dedicated cervical MRI of the arterial wall. METHODS: The study was -approved by the Ethics Committee of Ile de France III. Informed consent was waived. The manuscript was prepared in accordance with the STROBE statement. Fast spin-echo T1-weighted fat-suppressed axial sequences were performed at admission (MRI1) and during the first week after initiation of the treatment (MRI2). Two readers measured volumes, craniocaudal length of the mural hematoma and lumen patency, and searched for early recurrent CAD. They also searched for extension or recurrence of ischemic brain lesions and for hemorrhagic transformation on diffusion-weighted imaging (DWI) and gradient echo T2 (T2*) sequences, respectively. RESULTS: The population included 44 patients (31 in groupAC, 13 in groupAP) with 49 CAD (35 carotid, 14 vertebral). Recurrent CAD and reduction of the lumen did not occur in either group. We did not observe recurrent DWI lesions or occurrence of hemorrhagic transformation. Interobserver agreement [intraclass correlation coefficient (95% CI)] was excellent for volume measurement [0.98 (0.97-0.99) and 0.99 (0.98-1.0) for volume1 and volume2, respectively]. While mean volumes and length of the mural hematoma decreased after treatment in both groups (volume: groupAC -13 ± 22%, groupAP -12 ± 24%, p = 0.33; length: groupAC -10 ± 27%, groupAP -10 ± 20%, p = 0.18), approximately one third of patients in each group had some growth of the mural hematoma as well as an increase in length. CONCLUSION: Limited growth of the mural hematoma was seen with both treatments in approximately one third of patients during the first week after treatment initiation. However, neither AC nor AP agents promote reduction of the lumen or recurrent dissection.


Subject(s)
Anticoagulants/therapeutic use , Aortic Dissection/drug therapy , Cervical Vertebrae/blood supply , Hematoma/drug therapy , Adult , Aortic Dissection/complications , Aortic Dissection/diagnosis , Anticoagulants/adverse effects , Female , France , Hematoma/diagnosis , Hematoma/etiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Observer Variation , Predictive Value of Tests , Recurrence , Reproducibility of Results , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
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